PoyD is a radical S-adenosyl methionine epimerase that introduces multiple D-configured amino acids at alternating positions into the highly complex marine peptides polytheonamide A and B. This novel post-translational modification contributes to the ability of the polytheonamides to form unimolecular minimalistic ion channels and its cytotoxic activity at picomolar levels. Using a genome mining approach we have identified additional PoyD homologues in various bacteria. Three enzymes were expressed in E. coli with their cognate as well as engineered peptide precursors and shown to introduce diverse D-amino acid patterns into all-L peptides. The data reveal a family of architecturally and functionally distinct enzymes that exhibit high regioselectivity, substrate promiscuity, and irreversible action and thus provide attractive opportunities for peptide engineering. A radical change: Radical S-adenosyl methionine (SAM) epimerases is a new family of architecturally and functionally distinct bacterial enzymes. Three members from cyanobacteria were shown to introduce diverse D-amino acid patterns into all-L peptides. Their high regioselectivity, substrate promiscuity, and irreversible action provide interesting opportunities for peptide engineering.
|Original language||English (US)|
|Number of pages||5|
|Journal||Angewandte Chemie - International Edition|
|State||Published - Aug 4 2014|
- D -amino acids
- natural products